Introduction

Covering the same period as the previous mesoderm lecture, lets now look at changes to the ectoderm.

The ectoderm will from the entire nervous system (both central and peripheral), the epidermis of the skin and in the head region specialised placodes.

Development of the epidermis (integumentary) and sensory placodes (sensory) and later development of neural, neural crest, will be covered in future topic specific lectures. The current lecture will also introduce the significance of environmental factors, such as maternal diet, to embryonic development.

I think this is the lecture with poor audio quality. While I do not have a Science Lecture available I have added the Medicine equivalent content. Note that the lecture slides from Dr Beverdam's lecture are the examinable theory content.

Human Neuralation - Early Stages

Carnegie stage 9 the three main divisions of the brain, which are not cerebral vesicles, can be distinguished while the neural groove is still completely open.

Carnegie stage 10 (two days later) neural folds begin to fuse near the junction between brain and spinal cord, when neural crest cells are arising mainly from the neural ectoderm.

Carnegie stage 11 (about 24 days) the rostral (or cephalic) neuropore closes within a few hours; closure is bidirectional, it takes place from the dorsal and terminal lips and may occur in several areas simultaneously. The two lips, however, behave differently.

Carnegie stage 12 (about 26 days) The caudal neuropore takes a day to close. Level of final closure is approximately at future somitic pair 31, corresponds to the level of sacral vertebra 2.

Secondary neurulation begins at stage 12 - is the differentiation of the caudal part of the neural tube from the caudal eminence (or end-bud) without the intermediate phase of a neural plate. Above text modified from[1]

Abnormalities

Neural Tube Defects (NTD)

Failure of neural tube closure either incorrectly or incomplete

Dysraphism is the term often used to describe the defective fusion of the neural folds. The position and degree of failure of fusion will result in either embryonic death or a range of different neural defects. The way (mode) in which the human neural tube fuses has been a source of contention. In humans, fusion appears to initiate at multiple sites but the mode is different from that found in many animal species used in developmental studies.

severity dependent upon level within the tube and degree of failure

caudal failure - spina bifida cranial failure - anancephaly

Maternal Diet

Folic acid and iodine fortification (2016)

Folate

Found that supplementation of maternal diet with folate reduces incidence of NTDs.

A randomised controlled trial conducted by the Medical Research Council of the United Kingdom demonstrated a 72% reduction in risk of recurrence by periconceptional (ie before and after conception) folic acid supplementation (4mg daily).

Women who have one infant with a neural tube defect have a significantly increased risk of recurrence (40-50 per thousand compared with 2 per thousand for all births)

In the U.S.A. the Food and Drug Administration in 1996 authorized that all enriched cereal grain products be fortified with folic acid, with optional fortification beginning in March 1996 and mandatory fortification in January 1998. The data in the above graphs show the subsequent changes in anencephaly and spina bifida rate over that period.

Iodine

A second maternal diet requirement for later neural growth and development.

Iodine is required for fetal thyroid hormone synthesis.

Holoprosencephaly

Holoprosencephaly (HPE) is developmental abnormality where the forebrain does not divide into the two separate hemispheres and ventricles.

Critical Periods of Human Development

Exposure to teratogens during these "critical periods" results in specific abnormalities.

most systems are susceptible during embryonic development (first trimester)

the earlier the exposure the more severe the effects

each system has a different critical period

longest critical periods

longest developing systems (neural, genital)

complicated developmental origins (sensory systems)

The table below identifies approximate windows of time, "critical periods", that following exposure to teratogens can lead to developmental abnormalities (anomalies, congenital). In general, the effects for each system are more severe (major anomalies) in the embryonic period during organogenesis in the first trimester. Later teratogen exposure are less severe (minor anomalies) in the fetal period during continued growth and differentiation in the second and third trimester.

diencephalon - the caudal portion of forebrain after it divides into 2 parts in the 5 secondary vesicle brain (week 5). (cavity- 3rd ventricle) Forms the thalmus and other nuclei in the adult brain. (sc-My-Met-Mes-Di-Tel)

dorsal root ganglia - (spinal ganglia) sensory ganglia derived from the neural crest lying laterally paired and dorsally to the spinal cord (in the embryo found ventral to the spinal cord). Connects centrally with the dorsal horn of the spinal cord.

dura mater- "tough" (Latin, mater = mother) used in reference to the tough outer layer of the brain meninges.

efferent - refers to the direction of conduction from the central nervous system toward the periphery. Afferent is in the opposite direction.

ependyma - epithelia of remnant cells after neurons and glia have been generated and left the ventricular zone.

floorplate - early forming thin region of neural tube closest to the notochord.

ganglia - (pl. of ganglion) specialized neural cluster within either the CNS or PNS.

glia - supporting, non-neuronal cells of the nervous system. Generated from the same neuroepithelial stem cells that form neurons in ventricular zone of neural tube. Form astrocytes, oligodendrocytes.

grey matter - neural regions containing cell bodies (somas) of neurons. In the brain it is the outer layer, in the spinal cord it is inner layer. (see white matter white matter).

growth factor - usually a protein or peptide that will bind a cell membrane receptor and then activates an intracellular signaling pathway. The function of the pathway will be to alter the cell directly or indirectly by changing gene expression. (eg SHH).

hydrocephalus - abnormality as the result of an imbalance between the rate at which the CSF is being formed and the rate at which the CSF is passing through the arachnoidal villi back into the blood (hydrocephalus rate is a function of the degree of imbalance in these two). Very small imbalance exhibit subtle, if any, symptoms. Large imbalances will have rapidly evolving symptoms of unmistakable import.

mantle layer - layer of cells generated by first neuroblasts migrating from the ventricular zone of the neural tube. Layers are rearranged during development of the brain and spinal cord. (Ven-Man-Mar-CP)

neuromere - (prosomere) the model units for segmental brain development regions based upon a series of neural tube transverse subunits.

neuron - The cellur "unit" of the nervous system, transmitting signals between neurons and other cells. The post-mitotic cells generated from neuroepithelial stem cells (neuroblasts) in ventricular zone of neural tube.

neuropore - opening at either end of neural tube cranial (rostral, anterior) neuropore closes (day 25) about 2 days before caudal (posterior) that closes at somite level 32 to 34. Neural Tube Defects (NTDs) can be due to failure of these two neuropores to close.

optic nerve - (cranial nerve II, CN II) retinal ganglion neurons project from the retina as a tract into the brain (at the level of the diencephalon) associated with vision.

optic vesicle - diencephalon region of neural tube outgrowth that forms the primordia of the retina associated with vision.

otocyst - (otic vesicle) sensory placode that sinks into mesoderm to form spherical vesicle (stage 13/14 embryo) that will form components of the inner ear associated with hearing.

pars - (L. part of)

pharyngeal arch - (branchial arch, Gk. gill) form the main structures of the head and neck. Humans have 5 arches appearing in week 4 that form 4 external swellings, each arch has a pouch, membrane and cleft.

pharynx - uppermost end of GIT, beginning at the buccopharyngeal membrane and at the level of the pharyngeal arches.

prosomere - (neuromere) a model for segmental brain development based upon a series of neural tube transverse subunits. PMID 12948657

Rathke's pouch - a portion of the roof of the pharynx pushes upward towards the floor of the brain forming the anterior pituitary (adenohypophysis, pars distalis, pars tuberalis pars intermedia). Where it meets a portion of the brain pushing downward forming the posterior pituitary (neurohypophysis, pars nervosa). Rathke's pouch eventually looses its connection with the pharynx.

sonic hedgehog - (shh) secreted growth factor that binds patched (ptc) receptor on cell membrane. SHH function is different for different tissues in the embryo. In the nervous system, it is secreted by the notochord, ventralizes the neural tube, inducing the floor plate and motor neurons.

telencephalon - the cranial portion of forebrain after it divides into 2 parts in the 5 secondary vesicle brain (week 5). (cavity- lateral ventricles and some of 3rd ventricle) Forms the cerebral hemispheres in the adult brain. (sc-My-Met-Mes-Di-Tel)

ventricles - the fluid-filled interconnected cavity system with the brain. Fluid (cerebrospinal fluid, CSF) is generated by the specialized vascular network, the choroid plexus. The ventricles are directly connected to the spinal canal (within the spinal cord).